Describe the series of events leading to atherosclerosis.

Atherosclerosis is a cardiovascular disease where fatty, cholesterol filled plaque builds up in the arteries, it is the main contributor to coronary artery disease. These plaques narrow the vessel and obstruct blood flow.Risk factors for atherosclerosis include high cholesterol levels, obesity, hypertension, smoking, ageing and genetic predisposition. Irritants in the blood (for example high levels of LDL and toxins from cigarette smoke) trigger the beginning of atherosclerotic plaques, as together with hypertension they cause damage to the endothelium. Cholesterol in the blood begins to collect under the damaged endothelium and forms fatty streaks. These fats become oxidised which triggers a signal to the immune system. The immune system responds as monocytes are attracted to the damaged endothelium by chemotaxis. White blood cells try to degrade the cholesterol deposits, monocytes develop into macrophages as they begin to degrade the plaques. Most macrophages die during this process as they now contain too much cholesterol and transform into foam cells. Atherosclerosis is primarily an inflammatory disease, as macrophages die there is more signalling to the immune system (via cytokines) which then recruits more white blood cells to the site of damage. As these macrophages die and become foam cells they continue the cascade effect. During this inflammatory cascade, more and more endothelial cells get damaged and more fatty plaques accumulate. Calcium crystals accumulate as foam cells die, hardening the plaques, and as smooth muscle cells are exposed by the damaged endothelium they form a fibrous cap over the plaques to prevent inappropriate blood clotting further solidifying plaques. Plaque build up narrows the vessel and reduces elasticity, both contributing to hardening of the arteries. If fatty plaques rupture there can be a complete blockage of the artery as thrombogenic (clot forming) material gets exposed to the blood leading to thrombosis and eventually stroke or myocardial infarction.